Biomedical subjects

L Isaac

Publications and source records attributed to L Isaac.

At least 55 records · Page 3Linked to original sources

PubMed1988

Influence of dynorphin (1-13) on spinal reflexes in the rat.

Previously, we showed that intrathecal administration of dynorphin A (1-13) (dynorphin) in rats produced, within 5 min, a reversible inhibition of tail-shock vocalization, a reversible hind-limb paralysis and an irreversible loss of the tail-flick reflex. The selective loss of the tail-flick reflex was investigated using electrophysiologic methods and a dose of dynorphin effective in 90% of the rats. These studies revealed that intrathecal administration of dynorphin resulted in loss of the C-fiber initiated reflex when assayed 1 to 30 days after injection. On the other hand, reflexes initiated by Group I and III afferents were not obviously different from those seen in saline-injected animals. Application of dynorphin in situ on to the cord during stimulation of the dorsal root and recording of ventral root potentials demonstrated a rapid onset of peptide action. Initially the C-fiber evoked reflex was potentiated selectively with a decrease in conduction time. These responses were followed by inhibition of all reflexes for a short period of time after which the reflexes initiated by Group I and III afferents reappeared whereas the C-fiber reflex did not recover. This time course paralleled closely the time course of the loss of the tail-flick reflex suggesting that the two effects may be causally related. Furthermore, the selective N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate applied directly to the spinal cord during recording resulted in a reversible inhibition of the C-fiber-initiated reflex.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1988

The IgM receptor in mouse peritoneal macrophages.

Purified samples of IgM free of IgG and alpha 2-macroglobulin contaminants were obtained from mice sera. Resident peritoneal mouse macrophages poorly phagocytose sheep red blood cells (E) sensitized with purified mouse IgM anti-E. Conversely 62.5% of thioglycollate-elicited macrophages and 10.11% of BCG stimulated peritoneal cells phagocytose IgM sensitized sheep red blood cells. The monomeric and polymeric forms of IgM blocked almost completely the phagocytosis of erythrocytes opsonized with homologous IgM molecules. These data clarifies the controversy concerning the homologous IgM receptor in mouse macrophages and further suggest that it may be used as a marker for macrophage stimulation or activation.

Animals↗

PubMed1987

Intrathecal dynorphin(1-13) results in an irreversible loss of the tail-flick reflex in rats.

Intrathecal injection of dynorphin produced a loss of the tail-flick reflex that lasted throughout the 14-day experimental period whereas, the inclined plane test of motor function and tail-shock vocalization recovered within an hour. An important aspect of the loss of the tail-flick reflex was that it was an all-or-none event. At any dose of tail-flick latency either remained unchanged when compared with pre-injection latencies or the latency was elevated to the cut off time of 14 s. The ED50's +/- S.E.M. for tail-flick, inclined plane and tail-shock vocalization were 65.4 +/- 5.0, 67.7 +/- 5.0 and 68.0 +/- 3.9 nmol respectively. Results from the hot-plate test revealed no statistical difference between saline and dynorphin injected animals one day following the injection. Animals injected with morphine sulphate s.c. lost the tail-flick reflex but completely recovered by 24 h. Histology of the spinal cord of animals treated with dynorphin 24 h prior to sacrifice revealed dead neurons primarily in the ventral horn with little or no damage in the dorsal horn. These data demonstrate that dynorphin(1-13) injected intrathecally results in a rather specific neurotoxic action in the spinal cord.

Animals↗

PubMed1987

Calcium antagonist binding in cat brain tolerant to electroconvulsive shock.

Cats subjected to daily (25-30 days) electroconvulsive shock (ECS) demonstrated an elevation of their electroconvulsive threshold or tolerance to ECS. [3H] Nitrendipine binding was measured to brain regions from non-tolerant (sham shocked) and ECS tolerant cats 24 hr following the last shock. ECS produced a significant increase (45%) in the density of [3H] nitrendipine binding sites in the cerebral cortex and a significant decrease (33%) in the apparent affinity of [3H] nitrendipine in the cerebellum. No changes in binding were observed in the hippocampus. The effects of ECS were also investigated in the rat, an animal not displaying tolerance to repeated ECS. [3H] Nitrendipine binding to rat brain was measured 10 min and 24 hr following one shock (acute) or ten shocks delivered transauricularly once daily (chronic). Twenty-four hours following chronic ECS, there was a significant increase (19%) and decrease (11%) in the density, but no change in the apparent affinity of [3H] nitrendipine binding sites in the cerebral cortex and hippocampus respectively. No significant change in [3H] nitrendipine binding was observed in rat cerebellum 24 hr following chronic ECS. There were no changes in [3H] nitrendipine binding in the cerebral cortex and hippocampus 10 min and 24 hr following acute ECS. These results indicate that ECS can alter [3H] nitrendipine binding to calcium channel linked dihydropyridine binding sites in the central nervous system. It is suggested that changes in [3H] nitrendipine binding in the cat cerebellum may be involved in the development of tolerance to ECS.

Animals↗

PubMed1986

Electroconvulsive shock increases endogenous monoamine oxidase inhibitor activity in brain and cerebrospinal fluid.

Chronic daily administration of electroconvulsive shock (ECS) to cats resulted in a progressive elevation of seizure threshold which was accompanied by a sustained elevation in the activity of an endogenous monoamine oxidase inhibitor (EMAOI) present in cerebrospinal fluid (CSF). The increase in EMAOI activity in CSF following chronic ECS was observed maximally at 24-48 h. In rats, a single application of ECS resulted in a rapid but short-lasting increase in EMAOI activity present in the crude membrane fraction from brain. These findings demonstrate that both acute and chronic ECS modify the activity of an EMAOI in brain and CSF which may contribute to both the antidepressant and anticonvulsant effects of ECS treatment.

Animals↗

PubMed1986

Penetration of subarachnoid contrast medium into rabbit spinal cord. Comparison between metrizamide and iohexol.

The penetration into rabbit spinal cord of two nonionic contrast media, iohexol and metrizamide, and a reference tracer, technetium DTPA, were compared. The spinal subarachnoid space was perfused for 4 hours with a CSF solution to which technetium DTPA and either iohexol or metrizamide had been added. The contrast media and technetium DTPA concentrations reached a plateau level in CSF outflow within 80 minutes. The contrast media concentrations in CSF were higher than the technetium DTPA (P less than .001). In the cord tissue, technetium DTPA reached higher concentrations than the contrast media (P less than .001), and iohexol reached higher concentrations relative to technetium DTPA than metrizamide (P less than .001). The mean contrast media distribution volumes in the thoracic cord were 13% (iohexol) and 12% (metrizamide). The smaller distribution volume observed for metrizamide could be related to the larger effective size of "associated" metrizamide molecules or an interference with diffusion perhaps related to binding to glucose carriers.

Animals↗

PubMed1986

Iopamidol and neural tissue metabolism. A comparative in vitro study.

Metrizamide was the first water-soluble contrast medium with a neurotoxicity low enough to allow it to be used routinely in the entire subarachnoid space. However, neurologic complications are still observed in some patients following the use of metrizamide. The cause of this toxicity has not been established, but existing evidence suggests an interference with glucose metabolism. In previous studies, a depression in CO2 production in neural tissue slices was demonstrated when isotonic metrizamide was added but not isotonic iohexol. In addition to iohexol, there is another new, nonionic, monomeric, water-soluble CM, iopamidol, soon to be released for clinical use in the United States. Iopamidol, like iohexol, has shown fewer adverse reactions and seems to be safer for myelography than metrizamide. Direct comparative studies of iopamidol and iohexol are sparse and the cause of their toxicity is not yet understood. This study was performed to determine the effect of iopamidol on neural tissue glucose metabolism as compared with the effects of iohexol and metrizamide. Metrizamide decreased CO2 production in neural tissue slices by 23%. Iopamidol and iohexol did not produce significant depression. Moreover, this model could not demonstrate any significant difference between iopamidol and iohexol in direct comparisons. The new monomeric contrast media, iopamidol and iohexol, thus do not appear to interfere with glucose metabolism. Adverse reactions to these new media are most likely caused by other mechanisms.

Animals↗

PubMed1986

The effect of subarachnoid metrizamide and iohexol on cerebral glucose metabolism in vivo.

We studied the effect of metrizamide and iohexol on local cerebral glucose utilization (LCGU) using autoradiography. Metrizamide or iohexol was introduced into the subarachnoid space of rabbits and positioned over the right hemisphere for 3 or 6 hours. Using the unexposed (left) hemisphere as an internal control, we calculated relative changes in LCGU. In the three metrizamide-exposed animals the LCGU was decreased over the contrast media-exposed right temporoparietal cortex (L-R difference was positive). There was no significant changes in LCGU and no positive L-R difference after treatment with iohexol (three animals). We conclude that metrizamide does affect glucose metabolism in vivo, and this effect is dependent on localization of the contrast medium. The clinically safer drug, iohexol, in similar concentration and higher osmolality, did not decrease glucose metabolism.

Animals↗

PubMed1986

Enduring effects of prenatal diazepam on the behavior, EEG, and brain receptors of the adult cat progeny.

Pregnant cats were treated with a benzodiazepine receptor agonist, diazepam (DZ; Valium; average dose of 0.4 mg/kg/day, i.m.) between day 20 through day 53 of gestation in an attempt to alter the ontogenesis of the benzodiazepine receptors. As tested in fully developed one-year-old progenies, prenatal exposure to DZ resulted in a behavioral syndrome of hyperactivity, aggressiveness, behavioral signs of chronic anxiety, inability to habituate to novel environment, suppression or absence of the reward-induced alpha-like (7 to 11 Hz) electroencephalographic patterns during operantly conditioned behavior (bar pressing for 1 ml of milk reward), and deficits in the numbers of benzodiazepine receptors in the hypothalamus (-47%), fronto-orbital cortex (-33%) and postcentral cortex (-19%).

Agonistic Behavior↗

PubMed1985

Motor paralysis in rats after repeated electroconvulsive shock: comparison between aural and corneal stimulation.

Daily transaural electroshock treatment of rats results in a reversible hindlimb paralysis. Assuming there is a relationship between current pathway and the route of electroshock administration we compared both the type of convulsive behavior and the incidence of paralysis produced by transcorneal shock with that of transaural stimulation. Both transaural and transcorneal stimulation induced clonic and tonic convulsions, whereas, only transaural stimulation induced a body flexion (twisting and writhing). The use of transaural electrodes induced a higher incidence of paralysis than the use of corneal electrodes. These data demonstrate that both (1) the type of convulsive behavior produced and (2) the incidence of paralysis is related to electrode placement suggesting that paralysis is a function of current pathway.

Animals↗

PubMed1985

Prenatal exposure to diazepam results in enduring reductions in brain receptors and deep slow wave sleep.

After prenatal exposure to diazepam (Valium), mature rats at 4 months of age displayed slow wave sleep (SWS) electroencephalographic patterns indicating impaired synchronization and SWS mechanisms. These animals spent a much greater portion of their SWS in the lighter SWS I, as compared to the control group which showed a predominance of the deeper SWS II. At one year of age, the diazepam-exposed rats had much fewer diazepam-specific binding sites in the thalamus than the vehicle-exposed controls. These results provide first evidence for a physiological role for benzodiazepine receptors by showing that prenatal exposure to diazepam has an enduring and detrimental effect on their ontogenesis and sleep mechanisms.

Animals↗

PubMed1984

Reversible motor paralysis in rats after repeated electroconvulsive shock.

Repeated electroconvulsive shocks (ECS) delivered at brief (10 to 15 min) intervals through earclip electrodes, induced a reversible motor paralysis in 35% of treated rats. Paralysis was characterized by loss of locomotor activity without apparent loss of sensory functions. It occurred after 10 to 13 shocks regardless of whether stimulation was of subthreshold (40 to 60 mA) or suprathreshold (65 mA) intensity. This phenomenon may provide a useful animal model for the investigation of reversible injury to the spinal cord.

Animals↗

PubMed1984

Characterization of the binding of [3H]Ro 5-4864, a convulsant benzodiazepine, to guinea pig brain.

The density of high affinity binding sites for [3H]4'-chlorodiazepam [( 3H]Ro 5-4864) in guinea pig cerebral cortex is significantly higher (3.8-fold) than the density reported in the rat, and is nearly equal to the density of binding sites for other [3H]benzodiazepines (e.g., diazepam, flunitrazepam). The density of these [3H]Ro 5-4864 binding sites was generally higher in guinea pig brain than in rat brain, with the exception of olfactory bulb. Both the subcellular distribution and pharmacologic profile of these sites in guinea pig brain appears qualitatively similar to observations previously reported in the rat. The high density of binding sites for [3H]Ro 5-4864, coupled with the potency of this compound as a convulsant in the guinea pig, suggest this species will be a valuable model for elucidating putative pharmacologic and physiologic functions of these sites in brain.

Animals↗

PubMed1983

Alteration of electroconvulsive threshold by cerebrospinal fluid from cats tolerant to electroconvulsive shock.

Daily electroconvulsive shocks for 22 days resulted in a progressive elevation of electroconvulsive threshold. When these shocks were discontinued, the thresholds returned to untreated levels in approximately 20 days. Cerebrospinal fluid collected from cats with elevated thresholds and repeatedly transferred to the ventricular space of untreated animals elevated the electroconvulsive threshold of the recipient. This finding demonstrates that a substance present in the cerebrospinal fluid of cats with elevated electroconvulsive threshold can alter the threshold of untreated animals.

Animals↗

PubMed1983

Nociceptive assessment modifies behavioral tolerance without altering brain morphine concentration.

The influence of nociceptive assessment on the development of behavioral tolerance and on brain morphine concentration was examined in morphine pellet-implanted rats. Tolerance was facilitated by experience with the nociceptive tail flick test procedure, whereas whole brain opiate levels, determined by radioimmunoassay, were not altered by the behavioral tests. Parallel experiments with placebo-implanted rats indicate the significance of environmental context in nociception. These results demonstrate that behavioral manipulations can significantly modify pharmacological effects without altering drug concentration in the brain.

Analgesia↗

PubMed1983

Neither REM sleep deprivation nor rebound influences 3H-diazepam binding n rat brain.

Rats were placed on either small (subjected to REM sleep deprivation) or large circular platforms (stress controls) surrounded by water for 96 hours. Six animals from each group were either decapitated immediately following 96 hours or placed in cages and decapitated 6 hours later. Benzodiazepine receptor binding in rat brain cortices and brain stems was assessed using 3H-diazepam as the ligand. Scatchard analysis of these data showed that neither REM sleep deprivation nor REM sleep rebound affected the kinetics of 3H-diazepam binding (Bmax or apparent KD) in vitro.

Animals↗

PubMed1981

Brain sites for the antihypertensive action of clonidine.

In conclusion, I reviewed recent literature that directly investigated the site and mechanism of action of clonidine in the central nervous system. One can interpret these data in the following manner. In the medulla, clonidine is acting as an alpha-adrenergic receptor antagonist that inhibits excitatory input to the sympathetic nervous system. In the anterior hypothalamus, clonidine is acting as an alpha-adrenergic receptor agonist that excites an inhibitory pathway which inhibits excitatory input to the sympathetic nervous system. Both actions produce the same final response; that is, diminished sympathetic outflow from the central nervous system.

Afferent Pathways↗

PubMed1980

Clonidine in the central nervous system: site and mechanism of hypotensive action.

The data presented in this paper must be considered in conjunction with the fact that clonidine is both a partial alpha-adrenergic agonist and a partial alpha-adrenergic antagonist. In the anterior hypothalamus, clonidine, acting as an alpha-agonist, excites a pathway that inhibits excitatory cardiovascular neurons. Thus, the effect of neurons from the nucleus tractus solitarii (NTS) in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the posterior hypothalmus, clonidine, acting as an alpha-antagonist, decreases excitation of excitatory cardiovascular neurons, or acting as an alpha-presynaptic agonist to decrease norepinephrine release, decreases excitation of excitatory cardiovascular neurons. Again the effect of neurons from the NTS in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the medulla, clonidine, acting as an alpha-antagonist, inhibits excitatory input to the sympathetic nervous system and thereby appears to enhance the excitatory vagal cardiac reflex and the inhibitory baroreceptor reflex. All of these actions produce the same final response: diminished sympathetic outflow from the CNS, which translates clinically into decreased arterial blood pressure. In addition, these sites and mechanisms of action provide a rational basis for the lack of orthostatic hypotension seen following clonidine and offer a possible mechanism of the post-treatment syndrome.

Animals↗